2-<(3-Methylsulfonyl)propyl>-1H-isoindole-1,3(2H)-dione | 98184-58-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-<(3-Methylsulfonyl)propyl>-1H-isoindole-1,3(2H)-dione
• 英文别名: methyl 3-(N-phthalylamino)propyl sulfone；2-(3-(Methylsulfonyl)propyl)isoindoline-1,3-dione；2-(3-methylsulfonylpropyl)isoindole-1,3-dione
• CAS: 98184-58-8
• 化学式: C₁₂H₁₃NO₄S
• 分子量: 267.306
• InChiKey: CSIJUHOYVCEFIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  79.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-<(3-Methylsulfonyl)propyl>-1H-isoindole-1,3(2H)-dione 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 3-(甲基磺酰基)丙烷-1-胺盐酸盐
  参考文献：
  名称：

  Synthesis of Novel Analogs of Acetyl Coenzyme A: Mimics of Enzyme Reaction Intermediates

  摘要：

  An improved method for the synthesis of analogs of coenzyme A (CoA) and its thioesters, which are modified in the thiol or thioester moiety, has been developed using a combination of chemical and enzymatic reactions, The enzymes catalyzing the last two steps of CoA biosynthesis were used to prepare a CoA analog (1c) in which an amide bond is replaced by a thioester bond and the thiol group is replaced by a methyl group. Reaction of 1c with a primary amine in aqueous solution results in aminolysis of the thioester linkage to form the desired CoA analog. Reaction with different amines permits the introduction of a variety of functional groups in place of the nor mal thiol or thioester group. This methodology has been used in the synthesis of five new analogs of acetyl-CoA in which the thioester sulfur is replaced by a methylene group and the acetyl group is replaced by carboxylate (14a), nitro (14b), carboxamide (14c), methyl sulfoxide (14d), and methyl sulfone (14e) groups. 14a-c were designed to mimic the possible enolate or enol intermediate in the reaction of citrate synthase and related enzymes. 14a and 14c are potent inhibitors of citrate synthase, with K-i values 1000- and 570-fold lower than the K-m for acetyl-CoA, respectively. CD titrations indicate that 14a and 14c have low affinity for citrate synthase in the absence of oxaloacetate, consistent with their recognition as enol or enolate analogs. 14b is a poor inhibitor of citrate synthase, with affinity slightly lower than that for acetyl-CoA. These results are consistent with generation of the enol form of acetyl-CoA as the nucleophilic intermediate in the reaction of citrate synthase. 14d and 14e were designed to mimic the tetrahedral intermediate or transition state in the reaction of chloramphenicol acetyltransferase and related acetyl-CoA-dependent acetyltransferases. Both compounds are poor inhibitors of chloramphenicol acetyltransferase, with affinities slightly lower than that of acetyl-CoA, indicating that these compounds are not good mimics of the enzyme-bound tetrahedral intermediate or transition state.

  DOI：

  10.1021/ja00090a014
• 作为产物：
  描述：

  N-phthaloyl methionine sulfone 以 丙酮 为溶剂， 生成 2-<(3-Methylsulfonyl)propyl>-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  Photochemistry of N-phthaloyl derivatives of methionine

  摘要：

  Photodecarboxylation of N-phthaloyl derivatives of methionine sulfoxide 1b and methionine sulfone 1c was observed in acetone as the major reaction. For 1a a fast electron transfer initiated cyclization which leads to the bicyclization product 3 (X-ray structure) was observed in the sensitized photolysis. Direct photolysis of 1a leads preferentially to the tricyclic product 4 and the decarboxylation product 5. The methionine methyl esters 6a-c showed electon transfer initiated cyclization (for 6a) and disproportionation (for 6b), whereas 6c proved to be photostable.

  DOI：

  10.1016/0040-4039(93)85100-b

文献信息

• Phosphoinositide 3-kinase inhibitor compounds and methods of use
  申请人：Folkes Adrian

  公开号：US20080039459A1

  公开（公告）日：2008-02-14

  Compounds of Formulas Ia and Ib, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia and Ib for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式Ia和Ib的化合物，包括立体异构体，几何异构体，互变异构体，溶剂化物，代谢物和其药学上可接受的盐，可用于抑制脂质激酶包括PI3K，并用于治疗由脂质激酶介导的癌症等疾病。公开了使用公式Ia和Ib的化合物用于哺乳动物细胞中的体外，体内和原位诊断，预防或治疗此类疾病或相关病理条件的方法。
• PHOSPHOINOSITIDE 3-KINASE INHIBITOR COMPOUNDS AND METHODS OF USE
  申请人：Castanedo Georgette

  公开号：US20110105464A1

  公开（公告）日：2011-05-05

  Methods of using compounds of Formula Ia and Ib for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  本文披露了使用Ia和Ib化合物的方法，用于哺乳动物细胞中的体外、体内和原位诊断、预防或治疗相关病理状况。
• Sato, Yasuhiko; Nakai, Hideo; Wada, Masao, Liebigs Annalen der Chemie, 1985, # 6, p. 1099 - 1118
  作者：Sato, Yasuhiko、Nakai, Hideo、Wada, Masao、Mizoguchi, Tomishige、Hatanaka, Yasumaru、et al.

  DOI：——

  日期：——
• SATO, YASUHIKO;NAKAI, HIDEO;WADA, MASAO;MIZOGUCHI, TOMISHIGE;HATAMAKA, YA+, LIEBIGS ANN. CHEM., 1985, N 6, 1099-1118
  作者：SATO, YASUHIKO、NAKAI, HIDEO、WADA, MASAO、MIZOGUCHI, TOMISHIGE、HATAMAKA, YA+

  DOI：——

  日期：——
• PHOSPHOINOSITIDE 3-KINASE INHIBITOR COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：Genentech, Inc.

  公开号：EP2046799A1

  公开（公告）日：2009-04-15